Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | http://ri.ufs.br/jspui/handle/riufs/12599 |
Resumo: | Cancer is the most widespread cause of illness on the planet. It is understood as a set of more than 100 cellular diseases, caused by mutations and changes in mechanisms of epigenetic regulation. Popular knowledge provides a basis for the use of several plants with antitumor potential and many patients associate their use with the standard treatments for cancer, however, ignoring the existence of possible drug interactions or potentiation of adverse effects. Particularly infused Matricaria recutita has been popularly used in association with chemotherapy. This study aimed to evaluate the effect of the association between Matricaria recutita and the antineoplastic drug 5-fluorouracil in the treatment of mice transplanted with sarcoma 180. For this purpose, the aqueous extract of Matricaria recutita (EAMR) was prepared from the inflorescences, whose chromatographic record detected the presence of flavonoids such as luteonin, quecertin, rutin, and phenolic compounds such as caffeic acid. In vitro cytotoxicity of EAMR was evaluated against 5 human tumor cell lines: prostate (PC-3), colon (HCT-116), breast adenocarcinoma (MCF-7), acute promyelocytic leukemia (HL-60) and glioblastoma (SNB-19), and non-malignant fibroblast (L929) through the MTT assay. EAMR showed no cytotoxic activity in any of the cell lines tested, with IC 50> 50 μg / mL. For the in vivo experiment, swiss mice divided into experimental groups were treated with vehicle solution (CTRL-), 5-FU 25 mg / kg / day (CTRL +), EAMR 100, EAMR 200, EAMR 100 + 5-FU and EAMR 200 + 5-FU (mg / kg / day), n = 07 per group. The EAMR was administered v.o. and 5-FU i.p for 7 days of treatment. Tumor Inhibition (IT) and toxicological, biochemical, hematological and histopathological parameters were analyzed. Treatment of the associated groups EAMR 100 + 5-FU and EAMR 200 + 5-FU reduced tumor growth, with inhibition percentages of 66.1% and 87.7%, respectively, by probable (p <0.05) synergism between its compounds. In relation to the toxicological parameters, there was a reduction in body mass from the 3rd day of treatment in the associated groups (-1.2 ± 0.3 and -1.3 ± 0.3 g, respectively) (p <0.05) , demonstrating the potentiation of 5-FU in the loss of body mass, in addition to the presence of diarrhea, mainly for the higher dose. There was alteration of the heart mass in the associated groups 100 and 200 (0.50 ± 0.01 and 0.51 ± 0.02g, respectively) (p <0.05); (0.23 ± 0.02, 0.31 ± 0.03, and 0.21 ± 0.02 g, respectively) (p <0.05) 0.05) without potentiating the effect; and reduction of hepatic mass in the EAMR200 + 5-FU group, but without elevation of hepatic enzymes. There was no potentiation of myelosuppression (leucopenia and thrombocytopenia) in the associated groups. Histopathological analyzes of the tumors showed reduction of mitoses and presence of apoptotic areas in the associated groups, as well as reduction of the extent of the white pouch in the spleen. The results of this study suggest that the association between Matricaria recutita and 5-FU potentiates the antitumor activity in a synergistic way, intensifying some adverse effects. |
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Santos, Sara Albuquerque dosCarvalho, Adriana Andrade2020-01-21T11:52:25Z2020-01-21T11:52:25Z2018-02-15SANTOS, Sara Albuquerque dos. Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180. 2018. 119 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2018.http://ri.ufs.br/jspui/handle/riufs/12599Cancer is the most widespread cause of illness on the planet. It is understood as a set of more than 100 cellular diseases, caused by mutations and changes in mechanisms of epigenetic regulation. Popular knowledge provides a basis for the use of several plants with antitumor potential and many patients associate their use with the standard treatments for cancer, however, ignoring the existence of possible drug interactions or potentiation of adverse effects. Particularly infused Matricaria recutita has been popularly used in association with chemotherapy. This study aimed to evaluate the effect of the association between Matricaria recutita and the antineoplastic drug 5-fluorouracil in the treatment of mice transplanted with sarcoma 180. For this purpose, the aqueous extract of Matricaria recutita (EAMR) was prepared from the inflorescences, whose chromatographic record detected the presence of flavonoids such as luteonin, quecertin, rutin, and phenolic compounds such as caffeic acid. In vitro cytotoxicity of EAMR was evaluated against 5 human tumor cell lines: prostate (PC-3), colon (HCT-116), breast adenocarcinoma (MCF-7), acute promyelocytic leukemia (HL-60) and glioblastoma (SNB-19), and non-malignant fibroblast (L929) through the MTT assay. EAMR showed no cytotoxic activity in any of the cell lines tested, with IC 50> 50 μg / mL. For the in vivo experiment, swiss mice divided into experimental groups were treated with vehicle solution (CTRL-), 5-FU 25 mg / kg / day (CTRL +), EAMR 100, EAMR 200, EAMR 100 + 5-FU and EAMR 200 + 5-FU (mg / kg / day), n = 07 per group. The EAMR was administered v.o. and 5-FU i.p for 7 days of treatment. Tumor Inhibition (IT) and toxicological, biochemical, hematological and histopathological parameters were analyzed. Treatment of the associated groups EAMR 100 + 5-FU and EAMR 200 + 5-FU reduced tumor growth, with inhibition percentages of 66.1% and 87.7%, respectively, by probable (p <0.05) synergism between its compounds. In relation to the toxicological parameters, there was a reduction in body mass from the 3rd day of treatment in the associated groups (-1.2 ± 0.3 and -1.3 ± 0.3 g, respectively) (p <0.05) , demonstrating the potentiation of 5-FU in the loss of body mass, in addition to the presence of diarrhea, mainly for the higher dose. There was alteration of the heart mass in the associated groups 100 and 200 (0.50 ± 0.01 and 0.51 ± 0.02g, respectively) (p <0.05); (0.23 ± 0.02, 0.31 ± 0.03, and 0.21 ± 0.02 g, respectively) (p <0.05) 0.05) without potentiating the effect; and reduction of hepatic mass in the EAMR200 + 5-FU group, but without elevation of hepatic enzymes. There was no potentiation of myelosuppression (leucopenia and thrombocytopenia) in the associated groups. Histopathological analyzes of the tumors showed reduction of mitoses and presence of apoptotic areas in the associated groups, as well as reduction of the extent of the white pouch in the spleen. The results of this study suggest that the association between Matricaria recutita and 5-FU potentiates the antitumor activity in a synergistic way, intensifying some adverse effects.O câncer é a causa de adoecimento que mais se expande no planeta. É entendido como um conjunto de mais de 100 doenças celulares, causado por mutações e alterações nos mecanismos de regulação epigenética. O conhecimento popular fornece base para o uso de diversas plantas com potencial antitumoral e muitos pacientes associam seu uso aos tratamentos padrões para o câncer, desconhecendo, entretanto, a existência de possíveis interações medicamentosas ou potencializações de efeitos adversos. Particularmente infusos da Matricaria recutita tem sido popularmente utilizados em associação com quimioterápicos. Esse estudo teve como objetivo avaliar o efeito da associação entre a Matricaria recutita e o fármaco antineoplásico 5-fluorouracil no tratamento em camundongos transplantados com o sarcoma 180. Para isso, o extrato aquoso da Matricaria recutita (EAMR) foi preparado a partir das inflorescências, cujo registro cromatográfico detectou a presença de flavonóides como luteonina, quecertina, rutina e compostos fenólicos como ácido caféico. A citotoxicidade in vitro do EAMR foi avaliada frente a 5 linhagens de células tumorais humanas: próstata (PC-3), cólon (HCT-116), adenocarcinoma de mama (MCF-7), leucemia promielocítica aguda (HL-60) e glioblastoma (SNB-19), e não maligna fibroblasto (L929) através do ensaio do MTT. O EAMR não apresentou atividade citotóxica em nenhuma das linhagens de células testadas, com CI50 >50 μg/mL. Para o experimento in vivo foram utilizados camundongos swiss divididos em grupos experimentais: tratados com solução veículo (CTRL -), 5-FU 25 mg/kg/dia (CTRL +), EAMR 100, EAMR 200, EAMR 100 + 5-FU e EAMR 200 + 5-FU (mg/kg/dia), n = 07 por grupo. O EAMR foi administrado v.o. e o 5-FU i.p durante 7 dias de tratamento. Foram analisados a Inibição Tumoral (IT) e parâmetros toxicológicos, bioquímicos, hematológicos e histopatológicos. O tratamento dos grupos associados EAMR 100 + 5-FU e EAMR 200 + 5-FU reduziu (p < 0,05) o crescimento do tumor, com percentuais de inibição de 66,1% e 87,7%, respectivamente, por provável sinergismo entre seus compostos. Em relação aos parâmetros toxicológicos, houve redução da massa corpórea a partir do 3º dia de tratamento nos grupos associados (-1,2 ± 0,3 e -1,3 ± 0,3 g, respectivamente) (p < 0,05), demonstrando a potencialização do 5-FU quanto à perda de massa corpórea, além da presença de diarreia, principalmente para a maior dose. Houve alteração da massa do coração nos grupos associados 100 e 200 (0,50 ± 0,01 e 0,51 ± 0,02g, respectivamente) (p < 0,05); atrofia esplênica nos grupos 5-FU, EAMR100 + 5-FU e EAMR200 + 5-FU (0,23 ± 0,02, 0,31 ± 0,03 e 0,21 ± 0,02 g, respectivamente) (p < 0,05), sem potencialização do efeito; e redução da massa hepática no grupo EAMR200 + 5-FU, porém sem elevação das enzimas hepáticas. Não houve potencialização da mielossupressão (leucopenia e plaquetopenia) nos grupos associados. As análises histopatológicas dos tumores mostraram redução de mitoses e presença de áreas apoptóticas nos grupos associados, como também redução da extensão da poupa branca no baço. Os resultados desse estudo sugerem que a associação entre a Matricaria recutita e o 5-FU potencializa a atividade antitumoral de forma sinérgica, intensificando alguns efeitos adversos.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Apoio a Pesquisa e à Inovação Tecnológica do Estado de Sergipe - FAPITEC/SESão Cristóvão, SEporCâncerInterações medicamentosasPlantas medicinaisAgentes antineoplásicosCamomilaAntitumoralToxicidadeMatricaria recutitaCancerToxicityDrug interactionsMedicinal plantsCIENCIAS BIOLOGICAS::FISIOLOGIAEvidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180Evidence of interaction between chamomile (Matricaria recutita) and 5-fluorouracil against antineoplastic activity in mice with sarcoma 180info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPós-Graduação em Ciências FisiológicasUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/12599/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALSARA_ALBUQUERQUE_SANTOS.pdfSARA_ALBUQUERQUE_SANTOS.pdfapplication/pdf3639273https://ri.ufs.br/jspui/bitstream/riufs/12599/2/SARA_ALBUQUERQUE_SANTOS.pdfe279a1785e4e754a59b1ce550116af17MD52TEXTSARA_ALBUQUERQUE_SANTOS.pdf.txtSARA_ALBUQUERQUE_SANTOS.pdf.txtExtracted texttext/plain256356https://ri.ufs.br/jspui/bitstream/riufs/12599/3/SARA_ALBUQUERQUE_SANTOS.pdf.txt58f4d28ae0fe4fb491849559f3f03b4cMD53THUMBNAILSARA_ALBUQUERQUE_SANTOS.pdf.jpgSARA_ALBUQUERQUE_SANTOS.pdf.jpgGenerated Thumbnailimage/jpeg1397https://ri.ufs.br/jspui/bitstream/riufs/12599/4/SARA_ALBUQUERQUE_SANTOS.pdf.jpg64275c57c1e6feab707ed13fcfc207d2MD54riufs/125992020-01-21 08:55:04.931oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2020-01-21T11:55:04Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180 |
dc.title.alternative.eng.fl_str_mv |
Evidence of interaction between chamomile (Matricaria recutita) and 5-fluorouracil against antineoplastic activity in mice with sarcoma 180 |
title |
Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180 |
spellingShingle |
Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180 Santos, Sara Albuquerque dos Câncer Interações medicamentosas Plantas medicinais Agentes antineoplásicos Camomila Antitumoral Toxicidade Matricaria recutita Cancer Toxicity Drug interactions Medicinal plants CIENCIAS BIOLOGICAS::FISIOLOGIA |
title_short |
Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180 |
title_full |
Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180 |
title_fullStr |
Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180 |
title_full_unstemmed |
Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180 |
title_sort |
Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180 |
author |
Santos, Sara Albuquerque dos |
author_facet |
Santos, Sara Albuquerque dos |
author_role |
author |
dc.contributor.author.fl_str_mv |
Santos, Sara Albuquerque dos |
dc.contributor.advisor1.fl_str_mv |
Carvalho, Adriana Andrade |
contributor_str_mv |
Carvalho, Adriana Andrade |
dc.subject.por.fl_str_mv |
Câncer Interações medicamentosas Plantas medicinais Agentes antineoplásicos Camomila Antitumoral Toxicidade Matricaria recutita |
topic |
Câncer Interações medicamentosas Plantas medicinais Agentes antineoplásicos Camomila Antitumoral Toxicidade Matricaria recutita Cancer Toxicity Drug interactions Medicinal plants CIENCIAS BIOLOGICAS::FISIOLOGIA |
dc.subject.eng.fl_str_mv |
Cancer Toxicity Drug interactions Medicinal plants |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::FISIOLOGIA |
description |
Cancer is the most widespread cause of illness on the planet. It is understood as a set of more than 100 cellular diseases, caused by mutations and changes in mechanisms of epigenetic regulation. Popular knowledge provides a basis for the use of several plants with antitumor potential and many patients associate their use with the standard treatments for cancer, however, ignoring the existence of possible drug interactions or potentiation of adverse effects. Particularly infused Matricaria recutita has been popularly used in association with chemotherapy. This study aimed to evaluate the effect of the association between Matricaria recutita and the antineoplastic drug 5-fluorouracil in the treatment of mice transplanted with sarcoma 180. For this purpose, the aqueous extract of Matricaria recutita (EAMR) was prepared from the inflorescences, whose chromatographic record detected the presence of flavonoids such as luteonin, quecertin, rutin, and phenolic compounds such as caffeic acid. In vitro cytotoxicity of EAMR was evaluated against 5 human tumor cell lines: prostate (PC-3), colon (HCT-116), breast adenocarcinoma (MCF-7), acute promyelocytic leukemia (HL-60) and glioblastoma (SNB-19), and non-malignant fibroblast (L929) through the MTT assay. EAMR showed no cytotoxic activity in any of the cell lines tested, with IC 50> 50 μg / mL. For the in vivo experiment, swiss mice divided into experimental groups were treated with vehicle solution (CTRL-), 5-FU 25 mg / kg / day (CTRL +), EAMR 100, EAMR 200, EAMR 100 + 5-FU and EAMR 200 + 5-FU (mg / kg / day), n = 07 per group. The EAMR was administered v.o. and 5-FU i.p for 7 days of treatment. Tumor Inhibition (IT) and toxicological, biochemical, hematological and histopathological parameters were analyzed. Treatment of the associated groups EAMR 100 + 5-FU and EAMR 200 + 5-FU reduced tumor growth, with inhibition percentages of 66.1% and 87.7%, respectively, by probable (p <0.05) synergism between its compounds. In relation to the toxicological parameters, there was a reduction in body mass from the 3rd day of treatment in the associated groups (-1.2 ± 0.3 and -1.3 ± 0.3 g, respectively) (p <0.05) , demonstrating the potentiation of 5-FU in the loss of body mass, in addition to the presence of diarrhea, mainly for the higher dose. There was alteration of the heart mass in the associated groups 100 and 200 (0.50 ± 0.01 and 0.51 ± 0.02g, respectively) (p <0.05); (0.23 ± 0.02, 0.31 ± 0.03, and 0.21 ± 0.02 g, respectively) (p <0.05) 0.05) without potentiating the effect; and reduction of hepatic mass in the EAMR200 + 5-FU group, but without elevation of hepatic enzymes. There was no potentiation of myelosuppression (leucopenia and thrombocytopenia) in the associated groups. Histopathological analyzes of the tumors showed reduction of mitoses and presence of apoptotic areas in the associated groups, as well as reduction of the extent of the white pouch in the spleen. The results of this study suggest that the association between Matricaria recutita and 5-FU potentiates the antitumor activity in a synergistic way, intensifying some adverse effects. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-02-15 |
dc.date.accessioned.fl_str_mv |
2020-01-21T11:52:25Z |
dc.date.available.fl_str_mv |
2020-01-21T11:52:25Z |
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info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SANTOS, Sara Albuquerque dos. Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180. 2018. 119 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2018. |
dc.identifier.uri.fl_str_mv |
http://ri.ufs.br/jspui/handle/riufs/12599 |
identifier_str_mv |
SANTOS, Sara Albuquerque dos. Evidência de interação entre a camomila (Matricaria recutita) e o 5-fluorouracil frente à atividade antineoplásica em camundongos com sarcoma 180. 2018. 119 f. Dissertação (Mestrado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2018. |
url |
http://ri.ufs.br/jspui/handle/riufs/12599 |
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por |
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Pós-Graduação em Ciências Fisiológicas |
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Universidade Federal de Sergipe |
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